Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N omega-nitro-L-arginine methyl ester (L-NAME) is commonly used as a selective inhibitor for in vivo studies of brain nitric oxide (NO) synthase. We aimed to study the fate of N omega-nitro-L-arginine [11C]methyl ester ([11C]L-NAME) using positron emission tomography in monkey and high performance liquid chromatography methods in dogs and rats. We found that [11C]L-NAME was rapidly (t1/2 = 2 min) metabolized into N omega-nitro-L-arginine (L-NA) and [11C]methanol which both had a slow rate of elimination. Although, in vivo, L-NAME administration leads to long-lasting NO synthase inhibition by L-NA, methanol which is a potent neurotoxin in primate may produce detrimental effects unrelated to NO synthase inhibition.
 ...
PMID:In vivo metabolites of N omega-nitro-L-arginine methyl ester: methanol and N omega-nitro-L-arginine. 874 3

N(omega)-nitro-L-arginine methyl ester (L-NAME) was labelled with carbon-11 as a potential PET tracer for NO synthase. N(alpha)-t-butoxycarbonyl-N(omega)-nitro-L-arginine was reacted with [11C]diazomethane. After deprotection with trifluoroacetic acid the formed [11C]L-NAME was purified using HPLC. Biodistribution studies in rats and PET studies in monkeys and dogs showed no correlation between radioactivity distribution and NO synthase localization in brain and heart. Substantial amounts of [11C]methanol were detected in dog plasma shortly after injection. These findings preclude the use of [11C]L-NAME as a PET tracer.
 ...
PMID:Synthesis and in vivo distribution of no-carrier-added N(omega)-Nitro-L-arginine [11C]methyl ester, a nitric oxide synthase inhibitor. 883 8

The effects of methanol on isolated segments of rat aorta were investigated. In the absence of any vasoactive agent, methanol (5-675 mM) failed to alter basal tension. In rat aortic rings precontracted with high K+ (30 mM), methanol elicited a concentration-related relaxation at concentrations of from 5 to 675 mM. The K+-induced contraction in the presence of endothelium was more strongly inhibited by methanol than in the absence of endothelium. The effective concentration producing approximately 50% of the maximal relaxation response (ED50) to methanol was about 96 mM. Methanol-induced relaxations could not be abolished either by 5 x 10(-5) M N-nitro-L-arginine methyl ester (L-NAME) or NG-nitro-L-arginine (L-NNA), both selective inhibitors of nitric oxide (NO) formation; these relaxations were not potentiated by addition of excess L-arginine. An inhibitor of prostanoid synthesis, indomethacin (10(-5) M), had no effects on methanol-induced relaxation. Removal of extracellular Ca2+ ([Ca2+]o) resulted in almost complete inhibition of the relaxant effects of methanol on rat aortic ring segments. Marked attenuation of the relaxation responses of intact arteries to methanol was obtained after buffering intracellular Ca2+ ([Ca2+]i) with 10 microM BAPTA-AM. In 5-hydroxytryptamine (5-HT, 2.5 microM)- or phenylephrine (PE, 0.1 microM)-precontracted rat aortic rings, methanol amplified contractile responses to 5-HT and PE; these increased responses were concentration dependent. No significant differences in these methanol potentiated responses were found between aorta with or without endothelial cells. The amplified rat aortic smooth muscle responses induced by methanol after PE could be modified only by phentolamine, an antagonist of PE, while responses to 5-HT could be inhibited by methysergide (an antagonist of 5-HT) and by phentolamine, diphenhydramine, and haloperidol. Pretreatment with 50, 200, and 500 mM methanol increased rat aortic contractile responses induced by 5-HT and PE. Our results suggest that: (a) acute methanol exposure relaxes rat aortic smooth muscle contractile responses induced by high K+, leading to vessel relaxation. This relaxation effect of methanol is endothelium-dependent, clearly Ca2+ dependent, and independent of endogenous vasodilators such as acetylcholine, histamine, catecholamines, serotonin, or PG. (b) Methanol seems to increase potassium current by shifting the potential towards more negative values in depolarized vascular muscle cell membranes, probably inducing hyperpolarization of the cell membranes leading to a repolarization. (c) In contrast to the relaxant responses, methanol potentiates contractile response of rat aorta to 5-HT and PE.
 ...
PMID:Differential effects of methanol on rat aortic smooth muscle. 974 53

Many drugs cannot be dissolved in distilled water and so other solvents such as ethanol, dimethylsulphoxide and methanol are used. Because very little is known about the direct effects of these three solvents on the cardiovascular system, we have examined their effects on isolated pulmonary and coronary arteries from the pig. Increasing concentrations of ethanol, dimethylsulphoxide and methanol induced relaxation in porcine pulmonary (at 1.2% v/v, 59.9+/-9.0% (n =9), 55.9+/-9.0% (n =6) and 12.3+/-6.4% (n = 8), respectively, of U46619-induced tone) and coronary arteries (at 1.2% v/v, 69.9+/-7.1% (n = 10), 78.9+/-6.1% (n = 7) and 12.9+/-8.2% (n = 6) respectively, of U46619-induced tone). In the pulmonary arteries the relaxation in response to ethanol was found to be endothelium-dependent whereas the responses to dimethylsulphoxide and methanol were unaffected by removal of the endothelium. In the coronary arteries the relaxation to all three solvents was independent of the presence of the endothelium. Comparison of the sensitivity of the tissues to the solvents showed that ethanol and dimethylsulphoxide produced comparative responses in both the pulmonary and coronary arteries, whereas methanol was much less potent. The endothelium-dependent response to ethanol in the porcine pulmonary artery (maximum response, Emax, 67.1+/-9.3% of U46619-induced tone, n = 7) was attenuated by the cyclooxygenase inhibitor, flurbiprofen (Emax 31.9 +/- 12.0%, n=7), the nitric oxide synthase inhibitor, L-NAME (NG-nitro-L-arginine methyl ester; Emax 23.5+/-10.2%, n = 7)) and the combination of both inhibitors (Emax 18.3+/-7.8%, n = 7). The residual relaxatory response to ethanol was abolished, and converted into a contractile response, both by removal of the endothelium (at 1.7% v/v ethanol 27.3+/-11.5% of U46619-induced tone, n=7) and by the addition of a low concentration of KC1 (49.9-/+10.3%, n=6), suggesting the release of a non-prostanoid, non-nitric oxide factor from the endothelium. This response, however, was not attenuated by the cannabinoid receptor-antagonist SR141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide HCL; 52.5-/+4.3% relaxation, n =8), suggesting that the factor released in this preparation by ethanol is not a cannabinoid. The results of this study indicate that many solvents commonly used in pharmacological experiments have pronounced vasoactive properties. Methanol might be the vehicle of choice, because it was the least active solvent, whereas high concentrations of ethanol might influence vascular function at both the level of the smooth muscle and the endothelium, with the action on the endothelium involving the release of endothelium-derived relaxing factors.
 ...
PMID:Endothelium-dependent relaxation in response to ethanol in the porcine isolated pulmonary artery. 975 53

Diesel exhaust particles (DEP) have been proved to induce serious pulmonary injury, among which lethal pulmonary edema has been assumed to be mediated by vascular endothelial cell damage. In the present study, we investigated the cytotoxic mechanism of DEP on human pulmonary artery endothelial cells focusing on the role of active oxygen species. Endothelial cell viability was assessed by WST-8, a novel tetrazolium salt. Nitric oxide (NO) production was measured by using a new fluorescence indicator, diaminofluorescein-2 (DAF-2). Organic compounds in DEP were extracted by dichloromethane and methanol. DEP-extracts damaged endothelial cells under both subconfluent and confluent conditions. The DEP-extract-induced cytotoxicity was markedly reduced by treatment with SOD, catalase, N-(2-mercaptopropionyl)-glycine (MPG), or ebselen (a selenium-containing compound with glutathione peroxidase-like activity). Thus superoxide, hydrogen peroxide, and other oxygen-derived free radicals are likely to be implicated in DEP-extract-induced endothelial cell damage. Moreover, L-NAME and L-NMA, inhibitors of NO synthase, also attenuated DEP-extract-induced cytotoxicity, while sepiapterin, the precursor of tetrahydrobiopterin (BH(4), a NO synthase cofactor) interestingly enhanced DEP-extract-induced cell damage. These findings suggest that NO is also involved in DEP-extract-mediated cytotoxicity, which was confirmed by direct measurement of NO production. These active oxygen species, including peroxynitrite, may explain the mechanism of endothelial cell damage upon DEP exposure during the early stage.
 ...
PMID:The cytotoxic effects of diesel exhaust particles on human pulmonary artery endothelial cells in vitro: role of active oxygen species. 1118 26

The effectiveness of Curcuma drugs against "Oketsu" and the differences in their efficacy were evaluated by examining their vasomotional effects as one index. Since nitric oxide (NO) is the relaxation factor of vascular smooth muscle and also an inhibitor of platelet aggregation in blood vessels, substances showing NO-dependent relaxation are thought to be effective in improving Oketsu. In this study, five Curcuma drugs derived from Curcuma longa, C. kwangsiensis, C. phaeocaulis, C. wenyujin, and C. zedoaria were used. Methanol extracts exhibited intense effects on relaxation in rings precontracted by prostaglandin F(2alpha) (PGF(2alpha)) despite pretreatment with and without N(G)-nitro-l-arginine methyl ester (L-NAME) as an inhibitor of NO synthesis. The maximal activities were approximately 80% at 10(-3) g/ml. From these methanol extracts, curcumin and eight sesquiterpenes were isolated. Since all these compounds showed NO-independent relaxation effects with almost the same intensities, the relaxation effects of Curcuma drugs can be estimated by the total amounts of curcumin and sesquiterpenes. Polysaccharides, the main constituents of methanol-insoluble compounds of water extracts, in contrast, showed contraction effects; only polysaccharides in C. zedoaria showed NO-dependent relaxation as well as contraction. All water extracts showed relaxation effects as sum of the methanol-soluble compounds-induced relaxation and polysaccharides-induced contraction. Therefore, all Curcuma drugs tested in the present study can be effective for vasodilation. Moreover, the drug derived from C. zedoaria has potential to cure Oketsu with its various acting points.
 ...
PMID:Effects of curcuma drugs on vasomotion in isolated rat aorta. 1291 65

In this investigation three bioactive compounds, responsible for the gastroprotective property of Amphipterygium adstringens, were purified from an active dichloromethane fraction. These compounds were 3alpha-hydroxymasticadienonic acid, beta-sitosterol and 3- epi-oleanolic acid. The latter was the most active compound (88.8 % of gastroprotection) followed by 3alpha-hydroxymasticadienoic acid and beta-sitosterol (69.8 and 42.5 % of gastroprotection, respectively). Carbenoxolone was used as positive control and it showed 88.4 % of gastroprotection. Masticadienonic acid was also isolated from the active fraction, but it was unable to inhibit the ethanol-induced gastric lesions. The gastroprotection of the methanol extract was completely inhibited by the pretreatment with l-NAME and attenuated by pretreatment with indomethacin and N-ethylmaleimide. These results suggest that endogenous nitric oxide plays an important role in the gastroprotection of A. adstringens methanol extract on ethanol-induced gastric mucosal lesions and that there is partial participation by prostaglandins and endogenous sulfhydryls. The effect of 3alpha-hydroxymasticadienonic acid was attenuated only by pretreatment with N-ethylmaleimide, indicating that endogenous sulfhydryls (thiols) participate in its gastroprotective mechanism. Capsaicin-sensitive afferent neurons do not participate in the gastroprotection of either the methanol extract or 3alpha-hydroxymasticadienoic acid.
 ...
PMID:Purification of gastroprotective triterpenoids from the stem bark of Amphipterygium adstringens; role of prostaglandins, sulfhydryls, nitric oxide and capsaicin-sensitive neurons. 1464 92

The methanol extract of Anacardium occidentale stem bark was evaluated for activities against the lipopolysaccharide (LPS)-induced septic shock, as well as LPS-induced microvascular permeability in mice. Pre-treatment with Anacardium occidentale extract (25-200 mg/kg) caused a dose-dependent and significant (p < 0.05) reduction in the elevated levels of alanine and aspartate aminotransferases in the sera of D-galactosamine-primed mice injected with LPS. The highest dose of the extract studied (200 mg/kg) produced a 100% protection against death from sepsis. Pentoxifylline (100 mg/kg) and L-NAME (5 mg/kg) offered 100% protection against LPS-induced septic shock, and produced marked reduction in elevated levels of transferases. A dose-related inhibition of LPS-induced microvascular permability in mice was also produced by pentoxifylline, L-NAME and the extract.
 ...
PMID:Effects of Anacardium occidentale stem bark extract on in vivo inflammatory models. 1550 26

The methanol extract of Sorbus commixta cortex (MSC) induced relaxation of the phenylephrine-precontracted aorta in a dose-dependent manner, which was disappeared by removal of functional endothelium. Pretreatment of the aortic tissues with N(G)-nitro-L-arginine methyl ester (L-NAME), methylene blue, or 1H-[1,2,4]-oxadiazole-[4,3-alpha]-quinoxalin-1-one (ODQ) inhibited the vascular relaxation induced by MSC. MSC-induced vascular relaxations were also markedly attenuated by addition of verapamil or diltiazem, while the relaxant effect of MSC was not blocked by pretreatment with indomethacine, glibenclamide, tetraethylammonium (TEA), atropine, or propranolol, respectively. Incubation of endothelium-intact carotid arteries or of human umbilical vein endothelial cells (HUVECs) with MSC increased the production of guanosine 3',5'-cyclic monophosphate (cGMP). Moreover, MSC-induced cGMP production was effect was blocked by pretreatment with L-NAME or ODQ. These results suggest that MSC dilates vascular smooth muscle via endothelium-dependent nitric oxide-cGMP signaling pathway, possible involvement of L-type Ca(2+) channel.
 ...
PMID:Vascular relaxation by the methanol extract of Sorbus cortex via NO-cGMP pathway. 1586 94

Chronic inhibition of nitric oxide (NO) synthesis by administration of high dose of N(G)-nitro-L-arginine methylester (L-NAME) induces vascular inflammation and subsequent atherosclerosis. We aimed to investigate whether the methanol extract of Sorbus commixta cortex (MSC) is able to prevent inflammatory process in a rat model of L-NAME-induced atherosclerosis. Chronic treatment with low or high doses of MSC prevented the L-NAME-induced increase in monocyte chemoattractant protein-1 (MCP-1) and nuclear factor-kappaB (NF-kappaB) p65 expressions as well as adhesion molecules including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in aorta. In addition, increased endothelin-1 (ET-1) and angiotensin converting enzyme (ACE) expressions and decreased endothelial cell NO synthase (ecNOS) expression in aorta from L-NAME treated group was reversed by treatment with MSC. From the histological examination, aortic segment from the L-NAME-treated rats revealed a thickening of intima and media, which was ameliorated by treatment with MSC. In conclusion, our results indicate that MSC can prevent atherosclerosis by inhibiting vascular over-expressions of vasoactive materials, pro-inflammatory transcription factor, and adhesion molecules and by augmenting ecNOS in chronic L-NAME-treated rat model.
 ...
PMID:Effect of methanol extract of Sorbus cortex in a rat model of L-NAME-induced atherosclerosis. 1599 6


1 2 3 4 5 Next >>